Endocrine Abstracts

Introduction: Heterozygous mutations of PAX6 gene are known to cause congenital eye abnormalities including aniridia. The gene is also required for islet cell development and mutations are associated with glucose intolerance. We report the case of a boy with known PAX6 mutation and aniridia who developed hyperglycaemia.

Case: A 15 year old boy presented to the emergency department with hyperglycaemia after reporting intermittent testicular discomfort to his GP. Hyperglycaemia had been noted several months previously on routine dermatology bloods and HbA1c taken a month before presentation was 66 mmol/mol. The patient denied any weight loss, but described several weeks of polyuria, polydipsia and tiredness. He had a background of bilateral aniridia, Peter’s anomaly and visual impairment. A de novo heterozygous nonsense PAX6 gene mutation c.607C>T p.(Arg203Ter) was identified soon after birth. He also has ADHD, ASD, acne and sleep disturbance. His medications include methylphenidate, aciclovir, isotretinoin and melatonin. There is a family history of thyroid disease and coeliac disease in maternal relatives. He was clinically well with blood glucose 12.2 mmol/l, pH 7.41 and ketones 0.2 mmol/l. His BMI was 30 kg/m² and he had bilateral aniridia but examination was otherwise unremarkable. He was commenced on multiple daily insulin and CGM. Subsequent results showed raised GAD (>250 units/ml) and IA-2 antibodies (25 IU/ml), normal ZnT8 (<10 U/ml), and raised C peptide (1,761 pmol/l). TPO antibodies were high (33.84 IU/ml) with normal TFTs and –ve TTG IgA antibodies. He was switched to Omnipod 5 and Dexcom, which aided his visual impairment. Three months post diagnosis he has a low insulin requirement (0.16 units/kg/day) with TIR around 70-80%.

Conclusion: This case describes new onset diabetes in a boy with a rare genetic mutation associated with monogenic diabetes, and positive type 1 diabetes autoantibodies. The PAX6 gene mutation may partly explain his glucose intolerance, which has been compounded by the development of type 1 diabetes. Further research is required to understand the clinical impact of PAX6 mutation on glucose tolerance and management options. Blood glucose levels should be monitored in patients with known PAX6 mutations.